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https://www.readbyqxmd.com/read/28735463/impact-of-pioglitazone-on-bone-mineral-density-and-bone-marrow-fat-content
#1
L M Pop, I Lingvay, Q Yuan, X Li, B Adams-Huet, N M Maalouf
Pioglitazone use is associated with an increased risk of fractures. In this randomized, placebo-controlled study, pioglitazone use for 12 months was associated with a significant increase in bone marrow fat content at the femoral neck, accompanied by a significant decrease in total hip bone mineral density. The change in bone marrow fat with pioglitazone use was predominantly observed in female vs. male participants. INTRODUCTION: Use of the insulin sensitizer pioglitazone is associated with greater fracture incidence, although the underlying mechanisms are incompletely understood...
July 22, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28735354/transplantation-sites-for-human-and-murine-islets
#2
Rebecca A Stokes, Kim Cheng, Amit Lalwani, Michael M Swarbrick, Helen E Thomas, Thomas Loudovaris, Tom W Kay, Wayne J Hawthorne, Philip J O'Connell, Jenny E Gunton
AIMS/HYPOTHESIS: Beta cell replacement is a potential cure for type 1 diabetes. In humans, islet transplants are currently infused into the liver via the portal vein, although this site has disadvantages. Here, we investigated alternative transplantation sites for human and murine islets in recipient mice, comparing the portal vein with quadriceps muscle and kidney, liver and spleen capsules. METHODS: Murine islets were isolated from C57BL6/J mice and transplanted into syngeneic recipients...
July 22, 2017: Diabetologia
https://www.readbyqxmd.com/read/28734833/transforming-growth-factor-beta-promotes-liver-tumorigenesis-in-mice-via-upregulation-of-snail
#3
Hyuk Moon, Hye-Lim Ju, Sook In Chung, Kyung Joo Cho, Jung Woo Eun, Suk Woo Nam, Kwang-Hyub Han, Diego F Calvisi, Simon Weonsang Ro
BACKGROUND & AIMS: Transforming growth factor beta (TGFB) suppresses early stages of tumorigenesis, but also contributes to migration and metastasis of cancer cells. A large number of human tumors contain mutations that inactivate its receptors, or downstream proteins such as Smad transcription factors, indicating that the TGFB signaling pathway prevents tumor growth. We investigated the effects of TGFB inhibition on liver tumorigenesis in mice. METHODS: C57BL/6 mice received hydrodynamic tail injections of transposons encoding HRAS(G12V) and a short hairpin RNA (shRNA) to downregulate p53, or those encoding HRAS(G12V) and MYC, or those encoding HRAS(G12V) and TAZ(S89), to induce liver tumor formation; mice were also given injections of transposons encoding SMAD7 or shRNA against SMAD2, SMAD3, SMAD4, or SNAI1 (Snail), with or without ectopic expression of Snail...
July 19, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28733876/human-papillomavirus-type-8-e7-protein-binds-nuclear-myosin-1c-and-downregulates-the-expression-of-pre-rrna
#4
Evelyn Oswald, Eileen Reinz, Renate Voit, François Aubin, Angel Alonso, Eeva Auvinen
Our aim was to search for new cellular binding partners for the E6 and E7 oncogenes of beta human papillomaviruses (HPV), whose direct role in skin carcinogenesis has not been thoroughly investigated. By employing glutathione S-transferase pulldown and coimmunoprecipitation, we identified nuclear myosin 1c as a binding partner of HPV 8 E7 protein. As nuclear myosin 1c is an essential component of the RNA polymerase I transcription complex, we studied the effects of HPV 8 E7 protein expression on ribosomal RNA (rRNA) expression...
July 21, 2017: Virus Genes
https://www.readbyqxmd.com/read/28733679/increased-overall-cortical-connectivity-with-syndrome-specific-local-decreases-suggested-by-atypical-sleep-eeg-synchronization-in-williams-syndrome
#5
Ferenc Gombos, Róbert Bódizs, Ilona Kovács
Williams syndrome (7q11.23 microdeletion) is characterized by specific alterations in neurocognitive architecture and functioning, as well as disordered sleep. Here we analyze the region, sleep state and frequency-specific EEG synchronization of whole night sleep recordings of 21 Williams syndrome and 21 typically developing age- and gender-matched subjects by calculating weighted phase lag indexes. We found broadband increases in inter- and intrahemispheric neural connectivity for both NREM and REM sleep EEG of Williams syndrome subjects...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733196/proteasome-subunit-beta-type-1-p11a-polymorphism-is-a-new-prognostic-marker-in-multiple-myeloma
#6
Gergely Varga, Gábor Mikala, Katalin Piroska Kiss, Éva Kosóczki, Edit Szabó, Nóra Meggyesi, Katalin Balassa, Petra Kövy, Bálint Tegze, Gergely Szombath, Attila Tordai, Hajnalka Andrikovics, László Homolya, Tamás Masszi
BACKGROUND: Proteasome subunit beta type 1 (PSMB1) rs12717 polymorphism, a single nucleotide polymorphism with unknown functional effect, was recently reported to influence response to bortezomib-based therapy in follicular lymphoma. PATIENTS AND METHODS: We retrospectively analyzed the prognostic impact of this polymorphism in 211 consecutively diagnosed multiple myeloma cases, and performed in vitro experiments to look into its functional consequences. RESULTS: On univariate analysis, patients carrying the variant G allele showed significantly shorter progression-free survival (PFS) with a pattern suggestive of a gene-dose effect (PFS 26...
June 30, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28733148/prevalence-and-predictors-of-pain-and-opioid-analgesic-use-following-total-pancreatectomy-with-islet-autotransplantation-for-pancreatitis
#7
Robert A Moran, Robert Klapheke, George K John, Sarah Devlin, Daniel Warren, Niraj Desai, Zhaoli Sun, Christi Walsh, Rita R Kalyani, Erica Hall, Ellen M Stein, Anthony N Kalloo, Atif Zaheer, Kenzo Hirose, Martin A Makary, Vikesh K Singh
BACKGROUND & OBJECTIVES: Total pancreatectomy with islet autotransplantation (TPIAT) is employed for the management of refractory pain in chronic pancreatitis (CP) with the prospect of partial beta cell preservation. The primary aim of this study is to evaluate the prevalence and predictors of abdominal pain and opioid use following TPIAT. METHODS: A single center cohort study of all adult patients who underwent TPIAT from 2011 to 2015 for CP. Postoperative pain outcomes included: opioid use, ongoing abdominal pain and new characteristic abdominal pain...
July 12, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28733034/decreased-expression-of-mir-150-mir146a-and-mir424-in-type-1-diabetic-patients-association-with-ongoing-islet-autoimmunity
#8
Guofeng Wang, Yong Gu, Ning Xu, Mei Zhang, Tao Yang
BACKGROUND: Recent studies revealed altered miRNAs profiling in patients with autoimmune diseases, including type 1 diabetes (T1D). Here, we conducted an observational study and examined the expression levels of these five miRNAs (miR-150,miR-146a,miR-424,miR-181a and miR-142-3P) in peripheral blood mononuclear cells (PBMCs) from T1D patients. METHODS: PBMCs were obtained from T1D cohorts (n = 78), type 2 diabetes (T2D, n = 46) and healthy control subjects (n = 56)...
July 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28732437/effect-of-microrna-21-transfection-on-in-vitro-differentiation-of-human-naive-cd4-t-cells-to-regulatory-t-cells
#9
Haideh Namdari, Mojgan Ghayedi, Jamshid Hadjati, Farhad Rezaei, Kurosh Kalantar, Parisa Rahimzadeh, Eisa Salehi
Regulatory T cells (Tregs) are important components of the immune system that modulate responses of other cells. These cells are involved in peripheral tolerance mechanisms, so defect in development and function of these cells can result in autoimmune disease. Increasing evidence supports the role of microRNAs-21 (miR-21) in the regulation of forkhead box P3 (Foxp3) expression in Tregs. We aimed to determine whether miR-21 transfection to naive CD4+ T cells can be useful in generation of iTregs in-vitro. We investigated in-vitro differentiation of miR-21-transfected naive CD4+ T cells to iTregs and compared these iTregs to cytokine-differentiated iTregs and control group...
June 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/28731364/synthesis-of-a-new-insulin-mimetic-anti-diabetic-drug-containing-vitamin-a-and-vanadium-iv-salt-chemico-biological-characterizations
#10
Abdel Majid A Adam, Ahmed M Naglah, Mohamed A Al-Omar, Moamen S Refat
Diabetes patients suffer from chronic disorders in the metabolism due to high blood sugar caused by anomalies in insulin excretion. Recently, vanadium compounds have been prepared and functionalized to decrease the level of hyperglycemia. Vitamin A boosts beta cell activity; therefore, the lack of this vitamin plays a role in the development of type 2 diabetes. The aim of this article focused on the synthesis of a new anti-diabetic drug formed from the complexation of a vanadium(IV) salt with vitamin A. Vitamin A acts as a unidentate chelate through the oxygen of its -OH group...
July 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/28730907/the-rs10229583-polymorphism-near-paired-box-gene-4-is-associated-with-gestational-diabetes-mellitus-in-chinese-women
#11
Tianyi Xu, Yiru Shi, Jiangbo Liu, Yun Liu, Ailin Zhu, Cui Xie, Yan Zhang, Yan Chen, Lirong Ren
Objective The rs10229583 polymorphism near paired box gene 4 ( PAX4) is associated with insulin resistance and type 2 diabetes. Mutations in the PAX4 gene may be associated with impaired differentiation/development of pancreatic islet beta cells during fetal development and, consequently, a compromised insulin response to high blood glucose. To ascertain whether this polymorphism plays a role in gestational diabetes mellitus (GDM), we investigated the genotypic and allele frequency differences between GDM and normal pregnancies...
January 1, 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28730558/transplantation-sites-for-porcine-islets
#12
Rebecca A Stokes, Denbigh M Simond, Heather Burns, Anita T Patel, Philip J O'Connell, Jenny E Gunton, Wayne J Hawthorne
AIMS/HYPOTHESIS: Xenotransplantation has great potential to provide beta cell replacement and thereby provide a cure for large numbers of people with type 1 diabetes. Crucial to the success of xenotransplantation is establishment of the most viable sites for transplantation. METHODS: We compared porcine islet tissue transplanted into kidney, liver and spleen in pig recipients as assessed by blood glucose levels and IVGTT. RESULTS: Kidney was the superior site for porcine islet tissue transplantation, followed by liver then spleen...
July 21, 2017: Diabetologia
https://www.readbyqxmd.com/read/28730310/optical-biosensor-optimized-for-continuous-in-line-glucose-monitoring-in-animal-cell-culture
#13
Mircea Tric, Mario Lederle, Lisa Neuner, Igor Dolgowjasow, Philipp Wiedemann, Stefan Wölfl, Tobias Werner
Biosensors for continuous glucose monitoring in bioreactors could provide a valuable tool for optimizing culture conditions in biotechnological applications. We have developed an optical biosensor for long-term continuous glucose monitoring and demonstrated a tight glucose level control during cell culture in disposable bioreactors. The in-line sensor is based on a commercially available oxygen sensor that is coated with cross-linked glucose oxidase (GOD). The dynamic range of the sensor was tuned by a hydrophilic perforated diffusion membrane with an optimized permeability for glucose and oxygen...
July 20, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28729889/differential-methylation-at-mhc-in-cd4-t-cells-is-associated-with-multiple-sclerosis-independently-of-hla-drb1
#14
Vicki E Maltby, Rodney A Lea, Katherine A Sanders, Nicole White, Miles C Benton, Rodney J Scott, Jeannette Lechner-Scott
BACKGROUND: Although many genetic variants have been associated with multiple sclerosis (MS) risk, they do not explain all the disease risk and there remains uncertainty as to how these variants contribute to disease. DNA methylation is an epigenetic mechanism that can influence gene expression and has the potential to mediate the effects of environmental factors on MS. In a previous study, we found a differentially methylation region (DMR) at MHC HLA-DRB1 that was associated within relapsing-remitting MS (RRMS) patients in CD4(+) T cells...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28729832/the-role-of-microglia-in-retinal-neurodegeneration-alzheimer-s-disease-parkinson-and-glaucoma
#15
REVIEW
Ana I Ramirez, Rosa de Hoz, Elena Salobrar-Garcia, Juan J Salazar, Blanca Rojas, Daniel Ajoy, Inés López-Cuenca, Pilar Rojas, Alberto Triviño, José M Ramírez
Microglia, the immunocompetent cells of the central nervous system (CNS), act as neuropathology sensors and are neuroprotective under physiological conditions. Microglia react to injury and degeneration with immune-phenotypic and morphological changes, proliferation, migration, and inflammatory cytokine production. An uncontrolled microglial response secondary to sustained CNS damage can put neuronal survival at risk due to excessive inflammation. A neuroinflammatory response is considered among the etiological factors of the major aged-related neurodegenerative diseases of the CNS, and microglial cells are key players in these neurodegenerative lesions...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28729115/arousal-and-drug-abuse
#16
REVIEW
Francisco J Urbano, Verónica Bisagno, Edgar Garcia-Rill
The reticular activating system (RAS) is not an amorphous region but distinct nuclei with specific membrane properties that dictate their firing during waking and sleep. The locus coeruleus and raphe nucleus fire during waking and slow wave sleep, with the pedunculopontine nucleus (PPN) firing during both waking and REM sleep, the states manifesting arousal-related EEG activity. Two important discoveries in the PPN in the last 10 years are, 1) that some PPN cells are electrically coupled, and 2) every PPN cell manifests high threshold calcium channels that allow them to oscillate at beta/gamma band frequencies...
July 17, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28728928/gtf-231-a-mixture-of-gymnemic-acid-trigonelline-and-ferulic-acid-significantly-ameliorates-oxidative-stress-in-experimental-type-2-diabetes-in-rats
#17
Roshana Devi Vellai, Sharmila Chandiran, Subramanian Sorimuthu Pillai
OBJECTIVES: According to a report by the United States National Health and Nutrition Examination Survey, nearly 60% of patients with diabetes have more than one complication caused by chronic diabetes. Type 2 diabetes is a multifactorial metabolic disorder that accounts for more than 95% of people with diabetes and usually requires multitargeted therapeutic interventions. It arises due to insufficient insulin secretion or its action or both. Recently, we reported that the oral administration of gymnemic acid, trigonelline and ferulic acid in the ratio of 2:3:1 (GTF-231), a mixture of 3 phytoingredients at a concentration of 300 mg/kg body weight significantly improved the glucose homeostasis in rats with low-dose streptozotocin-induced type 2 diabetes that were fed with high-fat diet...
July 17, 2017: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/28728415/-177-lu-labelled-cyclic-minigastrin-analogues-with-therapeutic-activity-in-cck2r-expressing-tumours-preclinical-evaluation-of-a-kit-formulation
#18
Christine Rangger, Maximilian Klingler, Lajos Balogh, Zita Pöstényi, Andras Polyak, Dariusz Pawlak, Renata Mikołajczak, Elisabeth von Guggenberg
Minigastrin (MG) analogues specifically target cholecystokinin-2 receptors (CCK2R) expressed in different tumours and enable targeted radiotherapy of advanced and disseminated disease when radiolabelled with a beta emitter such as (177)Lu. Especially truncated MG analogues missing the penta-Glu sequence are associated with low kidney retention and seem therefore most promising for therapeutic use. Based on [D-Glu1,desGlu2-6]MG (MG11) we have designed the two cyclic MG analogues cyclo1,9[γ-D-Glu1,desGlu2-6,D-Lys9]MG (cyclo-MG1) and cyclo1,9[γ-D-Glu1,desGlu2-6,D-Lys9,Nle11]MG (cyclo-MG2)...
July 20, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28728159/oxamate-enhances-the-anti-inflammatory-and-insulin-sensitizing-effects-of-metformin-in-diabetic-mice
#19
Mu-Chao Wu, Wei-Ran Ye, Yi-Jia Zheng, Shan-Shan Zhang
Metformin (MET) is the first-line drug for treating type 2 diabetes mellitus (T2DM). However, MET increases blood lactate levels in patients with T2DM. Lactate possesses proinflammatory properties and causes insulin resistance (IR). Oxamate (OXA), a lactate dehydrogenase inhibitor, can decrease tissue lactate production and blood lactate levels. This study was conducted to examine the effects of the combination of OXA and MET on inflammation, and IR in diabetic db/db mice. Supplementation of OXA to MET led to lowered tissue lactate production and serum lactate levels compared to MET alone, accompanied with further decreased tissue and blood levels of pro-inflammatory cytokines, along with better insulin sensitivity, beta-cell mass, and glycemic control in diabetic db/db mice...
July 21, 2017: Pharmacology
https://www.readbyqxmd.com/read/28727908/leveraging-a-clinical-phase-ib-proof-of-concept-study-for-the-gpr40-agonist-mk-8666-in-patients-with-type-2-diabetes-for-model-informed-phase-ii-dose-selection
#20
A W Krug, P Vaddady, R A Railkar, B J Musser, J Cote, Agh Ederveen, D G Krefetz, E DeNoia, A L Free, L Morrow, M V Chakravarthy, E Kauh, D A Tatosian, P A Kothare
GPR40 mediates free fatty acid-induced insulin secretion in beta cells. We investigated the safety, pharmacokinetics, and glucose response of MK-8666, a partial GPR40 agonist, after once-daily multiple dosing in type 2 diabetes patients. This double-blind, multisite, parallel-group study randomized 63 patients (placebo, n = 18; 50 mg, n = 9; 150 mg, n = 18; 500 mg, n = 18) for 14-day treatment. The results showed no serious adverse effects or treatment-related hypoglycemia. One patient (150-mg group) showed mild-to-moderate transaminitis at the end of dosing...
July 20, 2017: Clinical and Translational Science
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